3. What is Anaesthesia ???What is Anaesthesia ???
Anesthesia – is a reversible condition of comfort and
quiescence for a patient within the physiological limit
before, during and after performance of a procedure.
General anesthesia – for surgical procedure to
render the patient unaware/unresponsive to the
painful stimuli.
Drugs producing General Anaesthesia – are called General
Anaesthetics.
Local anesthesia - reversible inhibition of impulse
generation and propagation in nerves. In sensory
nerves, such an effect is desired when painful
procedures must be performed, e.g., surgical or
dental operations.
Drugs producing Local Anaesthesia – are called Local
Anaesthetics e.g. Procaine, Lidocaine and Bupivacaine etc.
5. DIFFERENCE BETWEEN GENERAL
ANAESTHESIA & LOCAL ANAESTHESIA
FEATURES Gen.Anaesthsia Local Anaesthsia
Site of action CNS Peripheral nerves
Area of body involved Whole body Restricted area
Consciousness Lost Unaltered
Care of vital functions Essential Usually not needed
Poor health patients Risky Safer
Use in non cooperative
patients
Possible Not possible
Major surgery Preferred Cannot be preferred
Minor surgery Not preferred preferred
6. LOCAL ANAESTHETICS
DEFINITION: are drugs which, when
applied directly to peripheral nervous
tissue, block the nerve conduction and
abolish all sensations in the part supplied
by the nerve without loss of consciousness.
7. FEATURES OF LOCAL
ANAESTHETICS
Should have quick onset of action
Should not be irritating to skin & mucous membranes
Duration of action must be long enough to allow desired
surgery to be completed
Should be effective on both injection & local application
Should have low Systemic toxicity
8. Should not cause any permanent damage on any
tissue.
Should be relatively free from producing allergic
reaction.
Should be stable in solution and readily undergo
biotransformation.
No LA in use today satisfy all of these criteria ,
however all anesthetics do meet a majority of
them.
Contd…
9. Chemistry
All local anesthetics are weak bases, they have
amphiphilic property
Consist of hydrophilic secondary or tertiary amine on
one side
Lipophilic aromatic residue on other side
Two are joined by an alkyl chain through an ester or
amide linkage
11. ADVANTAGE OF AMIDE LAs OVER
ESTER LAs
Produce more intense and longer lasting
anaesthesia .
Bind to α1 acid glycoprotein in plasma.
Not hydrolysed by plasma esterases.
Rarely causes hypersensitivity reaction.
12. CLASSIFICATION
1. INJECTABLE ANAESTHETIC:
LOW POTENCY, SHORT DURATION
procaine
chloroprocaine
INTERMEDIATE POTENCY AND DURATION
Lidocaine
prilocaine
HIGH POTENCY, LONG DURATION
tetracaine
bupivacaine
ropivacaine
dibucaine
15. MECHANISM OF ACTION OF LAs
LA blocks the nerve conduction by reducing entry
of Na+ through the voltage gated channels
Due to this, they block the initiation & propagation
of nerve impulse.
At higher doses it also blocks
1. Voltage gated Ca2+
channels
2. K+
channels
16. PHARMACOKINETICS
Absorption
Local anesthetics are absorbed when ingested.
Some local anesthetics may be absorbed in
toxic amounts after topical use.
Absorption after an injection depends on drug
solubility in lipid and in water, tissue vascularity
and local anesthetic and vasoconstrictor
effects on local circulation.
17. Distribution: amides-wide distribution –I.V-lipophilics
taken up by highly perfused organs-then moderately
perfused
Ester type- short plasma half life
Metabolism and excretion
Esters are hydrolyzed by plasma and liver esterases.
Longer-acting esters are often metabolized more
slowly.. Patients with altered pseudo-cholinesterase
activity may be highly sensitive to these drugs.
Amides are metabolized in the liver by cyp450.-N-
dealkylation then hydrolysis except prilocaine-
hydrolysis first-o toludine-can cause
methhamoglobinemia
18. Patients with severe hepatic damage or advanced
congestive heart failure may be unusually sensitive to
these drugs.
Some amides are partially excreted unchanged in the
urine.
Acidification can enhance excretion
PK properties of amide LAs :
19. PRECAUTIONS AND INTERACTIONS
Aspirate lightly to avoid intravascular injection.
Inject the LA slowly &take care not to exceed the
maximum safe dose, especially in children.
Propranolol may reduce metabolism of lidocaine and
other amide LAs by reducing hepatic blood flow.
Vasoconstrictor (Adr) containing LA should be
avoided for patients with ischemic heart disease,
cardiac arrhythmia, uncontrolled hypertension those
receiving β-blockers or tricyclic antidepressants
22. Application of a local anesthetic to nose, mouth, throat,
tracheobronchial tree, esophagus.
Onset & duration depends on the site, the drug, its
concentration and form.
Absorption of soluble LAs from mucous membrane is
rapid.
24. Injection of LA directly into tissue under the skin.
used primarily for surgical procedures.
LAs most frequently used are lidocaine (1%), bupivacaine
(0.25%), etidocaine(0.5-1%), ropivacaine(0.5-1%),
mepivacaine(1-3%) and prilocaine(1-4%).
mix with adrenaline (1:20000) to prolong the action.
26. Injected around nerve trunks so that area distal to
injection is anaesthetised and paralyzed.
- Choice of LA and concentration is mainly determined
by the required duration of action.
- Lidocaine for intermediate duration of action
- longer lasting anesthesia bupivacaine may be
selected.
27. Field block:
- produced by injecting the LA subcutaneously in the
surrounding area of nerve so that all nerves coming
to particular field are blocked.
- herniorrhaphy, appendicectomy, dental procedures,
scalp stitching, operations on forearms and legs etc.
-
- Larger area can be anaesthetized with lesser drug
compared to infiltration.
28. Nerve Block:
local anesthetic is injected around a nerve that leads to
the operative site.
Usually more concentrated forms of local anesthetic
solutions are used
eg: radial nerve block, ulner nerve block so on.
Nerve block lasts than field block or infiltration
anaesthesia.
Lidocaine (1.5%), mepivacaine(1.5%), bupivacaine (0.25-
0.35%) can be used.
30. spinal dural space is filled with semi liquid fat through
which nerve root travel.
Injected in this space- acts primarily on nerve roots
and small amounts permeates through intravertebral
foramina to produce multiple paravertebral blocks.
used to produce analgesia or anaesthesia in surgical
and obstretric.
Divided into 3 categories depending on site of action:
1. Thoracic:
2. Lumbar:
3. Caudal:
32. Injected into the subarachnoid space between L2-3 or
L3-4 of the spinal cord .
Suitable LA like lidocaine (3-5%), bupivacaine (0.5-
0.8%), tetracaine(0.3-0.5%).
Primary site of action is cauda equina rather than
spinal cord.
Used to anaesthetize lower abdomen and hind limbs.
33. Use of hyperbaric(in7.5-10% glucose) or hypobaric (in
distilled water) solution of LA .
proper positioning of the patient is also limiting the
block to the desired level.
Advantages over general anaesthesia are:
Safer
Produces good analgesia and muscle relaxation without
loss of consciousness.
Cardiac, pulmonary, renal disease and diabetic pose
less problem.
34. complication of spinal anaesthesia:
Respiratory paralysis
Hypotension
Headache
Cauda equina syndrome
Septic meningitis
Contraindications:
Hypotension & hypovolemia
Infant & childrens- control of level is difficult
Vertebral abnormalities - kyphosis
36. Also referred as Bier’s block & used for upper limb and
orthopedic procedures.
Regional analgesia produced within 2-5min and last till 5-
10min.
Only ¼ of the injected drug enters systemic circulation
when tourniquet is removed.
Bradycardia can occur and bupivacaine should not be
used because of higher cardio toxicity.
37. General anaesthetics (Defn.)General anaesthetics (Defn.)
General Anaesthetics are the drugs which
produce reversible loss of all modalities of
sensation and consciousness, or simply, a drug
that brings about a reversible loss of
consciousness.
Remember !!! These drugs are generally
administered by an anesthesiologist in order to
induce or maintain general anesthesia to facilitate
surgery.
General anaesthetics are – mainly inhalation or
intravenous.
Balanced Anaesthesia: A combination of IV
anaesthetics and inhaled anaesthetics.
38. What are the Drugs used as GA ?What are the Drugs used as GA ?
(Classification)(Classification)
Inhalation:
1. Gas: Nitrous Oxide
2. Volatile liquids:
Ether
Halothane
Enflurane
Isoflurane
Desflurane
Sevoflurane
Intravenous:
1. Inducing agents:
Thiopentone,
Methohexitone sodium,
propofol and etomidate
1. Benzodiazepines (slower
acting):
Diazepam, Lorazepam,
Midazolam
1. Dissociative
anaesthesia:
Ketamine
1. Neurolept analgesia:
Fentanyl
39. Mechanisms of GA
For inhalation anesthetics – Minimum Alveolar Concentration (MAC)
– 1 (one) MAC is defined as the minimum alveolar concentration that
prevents movement in response to surgical stimulation in 50% of
subjects. Correlates with oil/gas partition coefficient
Practically –
Alveolar concentrations can be monitored continuously by measuring end-tidal
anesthetic concentration using spectrometry
End point (immobilization) – can me measured.
Other end points – Verbal commands or memory etc.
For Intravenous agents – Potency of IV agent is defined as the free
plasma concentration (at equilibrium) that produces loss of response to
surgical incision in 50% of subjects.
Difficult to measure:
no available method to measure blood or plasma concentration
continuously
Free concentration at site of action cannot be determined
(MAC explains only capacity of anaesthetics to enter in CNS and
attain sufficient concentration, but not actual MOA)
40. Mechanisms of GA
For inhalation anesthetics – Minimum Alveolar Concentration (MAC)
– 1 (one) MAC is defined as the minimum alveolar concentration that
prevents movement in response to surgical stimulation in 50% of
subjects. Correlates with oil/gas partition coefficient
Practically –
Alveolar concentrations can be monitored continuously by measuring end-tidal
anesthetic concentration using spectrometry
End point (immobilization) – can me measured.
Other end points – Verbal commands or memory etc.
For Intravenous agents – Potency of IV agent is defined as the free
plasma concentration (at equilibrium) that produces loss of response to
surgical incision in 50% of subjects.
Difficult to measure:
no available method to measure blood or plasma concentration
continuously
Free concentration at site of action cannot be determined
(MAC explains only capacity of anaesthetics to enter in CNS and
attain sufficient concentration, but not actual MOA)
41. Modern theory on Mechanism ofModern theory on Mechanism of
General AnesthesiaGeneral Anesthesia
Mainly acts via interaction with membrane proteins
Different agents - different molecular mechanism
Major sites: Thalumus & RAS, Hippocampus and
Spinal cord
Major targets – ligand gated (not voltage gated) ion
channels
Important one – GABAA receptor gated Cl¯
channel complexes; examples – many inhalation
anesthetics, barbiturates, benzodiazepines and
propofol
Potentiate the GABA to open the Cl¯ channels
Also direct activation of Cl¯ channel by some inhaled anesthetics and
Barbiturates
42. 4 (Four) Stages and signs !!!
• Traditional Description of signs and stages
of GA - Also called Guedel`s sign
• Typically seen in case of Ether
• Slow action as very much lipid soluble
• Descending depression of CNS
• Higher to lower areas of brain are involve
• Vital centers located in medulla are paralyzed last
43. Stages of GAStages of GA
Stage I: Stage of AnalgesiaStage I: Stage of Analgesia
Starts from beginning of anaesthetic inhalation and
lasts upto the loss of consciousness
Pain is progressively abolished during this stage
Patient remains conscious, can hear and see, and
feels a dream like state
Reflexes and respiration remain normal
It is difficult to maintain - use is limited to short
procedures only
44. stages of GA – contd.
Stage II: Stage of Delirium and Excitement:
From loss of consciousness to beginning of regular respiration
Excitement - patient may shout, struggle and hold his breath
Muscle tone increases, jaws are tightly closed.
Breathing is jerky; vomiting, involuntary micturition or defecation may
occur.
Heart rate and BP may rise and pupils dilate due to sympathetic
stimulation.
No stimulus or operative procedure carried out during this stage.
Breatholding are commonly seen. Potentially dangerous responses
can occur during this stage including vomiting, laryngospasm and
uncontrolled movement.
This stage is not found with modern anaesthesia – preanaesthetic
medication, rapid induction etc.
45. stages of GA
– contd.
Stage III: Stage of Surgical anaesthesia
Extends from onset of regular respiration to
cessation of spontaneous breathing. This has
been divided into 4 planes:
Plane 1: Roving eye balls. This plane ends when
eyes become fixed.
Plane 2: Loss of corneal and laryngeal reflexes.
Plane 3: Pupil starts dilating and light reflex is lost.
Plane 4: Intercostal paralysis, shallow abdominal
respiration, dilated pupil.
46. stages of GA – contd.
Stage IV: Medullary / respiratoryStage IV: Medullary / respiratory paralysis
Cessation of breathing failure of
circulation death
Pupils: widely dilated
Muscles are totally flabby
Pulse is imperceptible
BP is very low.
47. Properties of GA
For Patient:
- Pleasant, non-irritating and should not cause nausea or
vomiting
- Induction and recovery should be fast
For Surgeon:
- analgesia, immobility and muscle relaxation
- nonexplosive and noninflammable
For the anaesthetist:
1. Margin of safety: No fall in BP
2. Heart, liver and other organs: No affect
3. Potent
4. Cheap, stable and easily stored
5. Should not react with rubber tubing or soda lime
6. Rapid adjustment of depth of anaesthesia should be
possible
49. 1. Diethyl ether (C2H5 – O – C2H5)
Colourless, highly volatile liquid with a
pungent odour. Boiling point = 35ºC
Produces irritating vapours and are
inflammable and explosive.
Pharmacokinetics:
- 85 to 90 percent is eliminated through lung
and remainder through skin, urine, milk and
sweat
- Can cross the placental barrier
50. Ether – contd.
Advantages
- Can be used without
complicated apparatus
- Potent anaesthetic and
good analgesic
- Muscle relaxation
- Wide safety of margin
- Respiratory stimulation
and bronchodilatation
- Does not sensitize the
heart to adrenaline
- No cardiac arrythmias
- Can be used in delivery
- Less likely hepato or
nephrotoxicity
Disadvantages
- Inflammable and
explosive
- Slow induction and
unpleasant
- Struggling, breath holding,
salivation and secretions
(drowning) - atropine
- Slow recovery – nausea
& vomiting
- Cardiac arrest
- Convulsion in children
- Cross tolerance – ethyl
alcohol
51. 2. Nitrous oxide/laughing gas
(N2O)
NH4NO3 (s) → 2 H2O (g) + N2O (g)
Colourless, odourless inorganic gas with
sweet taste
Noninflammable and nonirritating, but of low
potency
Very potent analgesic, but not potent
anaesthetic
Carrier and adjuvant to other anaesthetics –
70% + 25-30% + 0.2-2%
As a single agent used wit O2 in dental
extraction and in obstetrics
52. Nitrous oxide – contd.
Advantages:
- Non-inflammable and
nonirritant
- Rapid induction and
recovery
- Very potent analgesic
(low concentration)
- No effect on heart rate
and respiration – mixture
advantage
- No nausea and vomiting
– post anaesthetic not
marked
- Nontoxic to liver, kidney
and brain
Disadvantages:
Not potent alone
(supplementation)
Not good muscle relaxant,
not
Hypoxia, unconsciousness
cannot be produced without
hypoxia
Inhibits methionine
synthetase (precursor to
DNA synthesis)
Inhibits vitamin B-12
metabolism
Dentists, OR personnel,
abusers at risk
Gas filled spaces expansion
(pneumothorax) -
dangerous
53. 3. Halothane
Fluorinated volatile liquid with sweet odour, non-
irritant non-inflammable and supplied in amber
coloured bottle
Potent anaesthetic (if precise control), 2-4% for
induction and 0.5-1% for maintenance
Boiling point - 50ºC
Pharmacokinetics: 60 to 80% eliminated unchanged.
20% retained in body for 24 hours and metabolized
Delivered by the use of a special vapourizer
Not good analgesic or relaxants
Potentiates NM blockers
54. Halothane – contd.
Advantages:
- Non-inflammable and non-
irritant
- Abolition of Pharyngeal
and laryngeal reflexes –
bronchodilatation –
preferred in asthmatics
- Potent and speedy
induction & recovery
- Controlled hypotension
- Inhibits intestinal and
uterine contractions –
external or internal version
- Popular anaesthetic in
developig countries - can
be used in children for
induction and maintenance
and adult maintenance
Disadvantages:
- Special apparatus - vapourizer
- Poor analgesic and muscle relaxation
- Myocardial depression – direct depression of
Ca++ and also failure of sympathetic activity –
reduced cardiac output (more and more)
- Hypotension – as depth increases and
dilatation of vascular beds
- Heart rate – reduced due to vagal stimulation,
direct depression of SA node and lack of
Baroreceptor stimulation
- Arrythmia - Sensitize heart to Adrenaline
- Respiratory depression – shallow breathing
(PP of CO2 rises) assisted ventilation
- Decreased urine formation – due to decreased
gfr
- Hepatitis: 1 in 10,000
- Malignant hyperthermia: Abnormal Ryanodine
receptor
- Prolong labour
55. 4. Enflurane:
Non-inflammable, with mild sweet odour and boils at
57ºC
Similar to halothane in action, except better muscular
relaxation
Depresses myocardial force of contraction and
sensitize heart to adrenaline
Induces seizure in deep anaesthesia and therefore
not used now - Epileptiform EEG
Metabolism one-tenth that of halothane-- does not
release quantity of hepatotoxic metabolites
Metabolism releases fluoride ion-- renal toxicity
56. 5. Isoflurane:
Isomer of enflurane and have similar
properties but slightly more potent
Induction dose is 1.5 – 3% and maintenance
dose is 1 – 2%
Rapid induction (7-10 min) and recovery
By special vapourizer
57. Isoflurane – contd.
Advantages:
- Rapid induction and
recovery
- Good muscle relaxation
- Good coronary
vasodilatation
- CO maintained, HR
increased – beta receptor
stimulation
- Less Myocardial depression
than no myocardial
sensitization to adrenaline
- No renal or hepatotoxicity
- Low nausea and vomiting
- No dilatation of pupil and no
loss of light reflex in deep
anaesthesia
- No seizure and preferred in
neurosurgery
- Uterine muscle relaxation
Disadvantages:
- Pungent and respiratory
irritant
- Special apparatus
required
- Respiratory depression -
prominent
- Maintenance only, no
induction
- Hypotension - ß
adrenergic receptor
stimulation
- Costly
(Desflurane and
Sevoflurane ----- read
yourself)
58. Intravenous Anaesthetics:
For induction only
Rapid induction (one arm-
brain circulation time)
For maintenance not used
Alone – supplemented with
analgesic and muscle
relaxants
Intravenous:
Inducing agents:
Thiopentone,
Methohexitone sodium,
propofol and etomidate
Benzodiazepines (slower
acting):
Diazepam, Lorazepam,
Midazolam
Dissociative
anaesthesia:
Ketamine
Neurolept analgesia:
Fentanyl
59. Thiopentone sodium:
Barbiturate: Ultra short acting
Water soluble
Alkaline
Dose-dependent suppression of CNS activity
Dose: 3-5mg/kg iv (2.5%) solution – 15 to 20 seconds
Pharmacokinetics:
- Redistribution
- Hepatic metabolism (elimination half-life 7-12 hrs)
- CNS depression persists for long (>12 hr)
60. Thiopentone – contd.
Advantages:
- Rapid induction
- Does not sensitize
myocardium to
adrenaline
- No nausea and vomiting
- Non-explosive and non-
irritant
- Short operations (alone)
Other uses: convulsion,
psychiatric patients and
narcoanalysis of cri
minals – by knocking off
guarding
Disadvantages:
- Depth of anaesthesia
difficult to judge
- Pharyngeal and
laryngeal reflexes
persists - apnoea –
controlled ventilation
- Respiratory depression
- Hypotension (rapid) –
shock and hypovolemia –
CVS collapse
- Poor analgesic and
muscle relaxant
- Gangrene and necrosis
- Shivering and delirium
61. Complications of anaesthesia:
During anaesthesia:
Respiratory depression
Salivation, respiratory
secretions
Cardiac arrhythmias
Fall in BP
Aspiration
Laryngospasm and asphyxia
Awareness
Delirium and convulsion
Fire and explosion
After anaesthesia:
Nausea and vomiting
Persisting sedation
Pneumonia
Organ damage – liver,
kidney
Nerve palsies
Emergence delirium
Cognitive defects
62. Important !
Drugs used in General Anaesthesia
Stages of General Anaesthesia with important points
in each stage
Details of Inhalation agents, mainly Ether, Halothane
and Isoflurane
Details of Inducing agents – Thiopentone and
Propofol
Dissociative anaesthesia – short question
Preanaesthetic medication and examples of Drugs
Viva and short questions - Second gas effect,
diffusion hypoxia, malignant hyperthermia and
Fentanyl
Notes de l'éditeur
Higher centres - Basal Ganglia, Cerebellum, Cerebrum, (including Cortex of the brain, & limbic System.
Lower centres - Brain stem (medulla oblongata, Pons and Mid Brain), Thalamus & Hypothalamus
PP of CO2 rises if respirtion is not assisted. Mismatch of perfusion-ventilation due to vasodilatation of hypoxic alveoli
This agent was used previously, but not now. It is faster acting substitute of Halothane. The features include -
These drugs are used as inducing agents and given via iv route. Produces loss of consciousness in one arm-brain circulation time (11 secs). These are not used for maintenance for the reasons – 1. Administration of multiple doses by i.v. injection or a continuous i.v. infusion can result in drug accumulation and delays in recovery from anesthesia. 2. The higher cost of i.v. therapy compared with the cost of inhaled therapy also is a consideration. 3. The lack of a means for continuously measuring the depth of anesthesia the most important reason for avoiding the use of i.v. anesthetics for anesthesia maintenance.